The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
THE INHIBITION OF THE ENZYMIC ACTIVITY OF BLOOD COAGULATION AND FIBRINOLYTIC SERINE PROTEASES BY A NEW LEUPEPTIN-LIKE INHIBITOR, AND ITS STRUCTURAL ANALOGUES, ISOLATED FROM STREPTOMYCES GRISEUS
CHENG-WU CHIHUA-ZHEU LIUCHI-YIN LIUBAKSHY A. K. CHIBBERFRANCIS J. CASTELLINO
Author information
JOURNALS FREE ACCESS

1989 Volume 42 Issue 10 Pages 1506-1512

Details
Abstract

A group of leupeptin analogues was found in Streptomyces griseus strain 254, isolated from a soil sample from Fujian Province, China. The inhibitors excreted in the culture filtrate were purified by adsorption on macroporous resin, followed by sequential ion exchange chromatography on DEAE-52 cellulose, CM-32 cellulose and affinity chromatography with immobilized trypsin. The preparation thus obtained was further purified by preparative HPLC. Several major components were found and characterized, which possessed different inhibitory properties toward trypsin. Based upon amino acid and mass spectrophotometric analysis, these peptides were placed in four major structural categories, viz., R-Val-Val-argininal, R-Leu-Leu-argininal, R-Ile-Ile-argininal and R-Thr-Thr-argininal, this latter component representing a newly identified leupeptin analogue. The structural variability of the R-group was partly responsible for the multiplicity of the peaks obtained with HPLC. All peptides displayed varying degrees of inhibitory activity toward proteases involved in blood coagulation and fibrinolysis, including plasmin, factor Xa, activated protein C and thrombin. Among these peptide inhibitors, the molecule containing threonine showed the strongest inhibitory activity.

Information related to the author
© Japan Antibiotics Research Association
Previous article Next article
feedback
Top